Affiliations: Clinical Oncology Laboratory, School of Medicine, University of Patras, Rio Patras, Greece | Department of Anatomy, School of Medicine, University of Patras, Rio Patras, Greece | Department of Surgery, School of Medicine, University of Patras, Rio Patras, Greece | Medical Research Council, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK | Institute of Immunology, Biomedical Sciences Research Center “Alexander Fleming”, Vari, Greece
Note: [] Corresponding author: Chariklia Petropoulou, Institute of Immunology, Biomedical Sciences Research Center “Alexander Fleming”, 34 Al. Fleming Street, 16672 Vari, Greece. Tel.: +30 210 9654465; Fax: +30 210 9653934; E-mail: [email protected].
Abstract: Background: The TGF-β signaling repressors SnoN and Ski have been critically implicated in human cancer. Methods: To explore the role of SnoN and Ski in the development and progression of colorectal cancer we examined their protein expression profile by immunohistochemistry in a series of human colorectal adenomas, carcinomas and lymph node metastases. The mRNA expression of SnoN was also quantified by Real-Time RT-PCR. Results: SnoN and Ski were overexpressed both in adenomas with severe dysplasia and colorectal carcinomas. Protein expression was cytoplasmic and nuclear with predominant cytoplasmic localization. The subcellular localization was related differently to pathologic variables of colorectal carcinomas. Although there was no significant association of protein levels with tumor invasion and metastasis, a significant correlation of nuclear SnoN and Ski with β-catenin pathway was observed. Moreover, SnoN mRNA did not differ in carcinomas as compared to normal control and there was no correlation between SnoN protein and mRNA levels. Conclusion: Our findings suggest that SnoN and Ski exert oncogenic effects in human colorectal carcinogenesis and their overexpression is implicated in early stage disease.
